Analysis of a test sample

ABSTRACT

An apparatus is disclosed which uses electrodes to analyse a test sample.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the U.S. national stage of PCT/GB2019/052246 filedAug. 9, 2019, which claims priority of United Kingdom patent application1813114.4 filed Aug. 10, 2018, both of which are hereby incorporated byreference in their entirety.

FIELD OF THE INVENTION

The present invention relates to a method and apparatus of analysis of atest sample. Particularly, but not exclusively, the present inventionrelates to a method and apparatus which can typically be used todetermine the proportion of living cells in a test sample.

BACKGROUND OF THE INVENTION

Capacitance measurement techniques are known for measuring thecapacitance (or specific capacitance or dielectric constant) of liquidsand suspensions, such as biological cells in ionic aqueous solutions.Known techniques involve introducing metal electrodes into the liquidand applying an excitation signal (usually sinusoidal) and measuringvoltage and current using a pair of measurement electrodes. Theimpedance, conductivity and specific capacitance or permittivity canthen be calculated. At high excitation frequencies (greater than about 1MHz) this is relatively straightforward with simple electrode andcircuit configurations. However at lower frequencies, and particularlywhere the conductivity is high (up to 100 mS/cm or so), theelectrode—liquid interface exhibits an impedance which appears in serieswith the impedance of interest and distorts the measurements.

EP1018025 discloses such a technique for measurement of biomass. Thisdocument describes the background to the Beta dispersion and howcorrection needs to be made for polarisation at measurement electrodes.

Electrode polarisation effects result largely from the chargedelectrodes attracting around themselves a counter layer of ions whichacts electrically as a capacitor/resistor network in series with thesuspension that is under measurement investigation. The magnitude of theelectrode polarisation effect is largely frequency dependent. To measurethe whole of the beta dispersion range (and alpha dispersion range)requires the use of a frequency region in which polarisation of themeasuring electrodes can contribute a significant capacitance which hasa material distortion on the measured capacitance. This error alsovaries with time as the electrode surface impedance is not stable anddepends upon electrode surface current density.

There have been numerous techniques developed for managing the inherenterrors in measurement of the impedance of the test sample. These includethe use of a four terminal layout and/or the careful choice of materialwhere the use of gold or platinum electrodes have been found to reducethe impedance between the electrode and test sample. However suchelectrodes are expensive and there remains some electrode/test sampleimpedance. A further technique is to increase separation between theelectrodes which means the impedance between the electrode and the testsample is less significant in comparison to the impedance of the testsample itself. In order to maximise the electrode separation,alternative probe configurations have been designed for carrying theelectrodes whereby for example electrodes are positioned on opposingfaces of an insulating finger meaning that the current flow path isaround a distal end of the probe finger, or even on opposite sides of acontaining vessel such as a fermenter.

Whilst the use of correction algorithms to differentiate between what wewish to measure and the interfering signals and techniques to manageelectrode polarisation are to some extent effective, it remains asignificant problem as the electrode polarisation impedance is notlinear, and is actually variable across the electrode surface and isfurther variable depending on the current density which in itself mayvary. Therefore the effect of electrode polarisation remains asignificant issue in analysis of a test sample.

SUMMARY OF THE INVENTION

According to the present invention there is an apparatus for analysis ofa test sample comprising:

-   -   a first electrode pair for application of an excitation current        to a test sample;    -   a measuring arrangement for measuring voltage through the test        sample comprising a second electrode pair; and    -   a receptacle for receipt of the test sample, where the        receptacle comprises a receptacle wall that forms a barrier        between the first and second electrode pair and the test sample        such that the receptacle wall contacts both the first and second        electrode pairs and the test sample when the apparatus is in an        operable state.

Thus, the excitation current is driven through the receptacle wall, testsample and receptacle wall between the first and second electrode pair.The voltage is measured through the receptacle wall, test sample andreceptacle wall again via the second electrode pair. In an alternativedefinition having the same meaning, voltage is measured across the testsample.

The four electrode arrangement mitigates against the variability whichis inherent in the two terminal arrangement.

The electrodes are therefore be positioned outside the receptacle inoperation, and there is no direct contact between the test sample andelectrodes in operation.

The test sample may be dielectric.

The measuring arrangement preferably further comprises an arrangement todetermine the current and voltage from the first and second electrodepair, and preferably has an extremely high input impedance which makesit possible to measure voltage whilst only causing only a small amountof current flow through the electrode's impedance. The voltage dropacross this impedance (which is proportional to electrode current andelectrode impedance) is then also very small and causes negligiblemeasurement errors when analysing the test sample.

The receptacle may comprise a flexible material. The receptacle maycomprise a polymeric bag, such as for example a blood bag.

The receptacle may be a bio-reactor, and may be configured for aspecific cell line. The receptacle may also be a bag fermenter. Suchsingle-use bioreactors have become established in modernbiopharmaceutical processes. Such bioreactors may be utilised asexamples only for mammalian cell culture, very demanding highcell-density or microcarrier-based processes. Such bioreactors typicallycomprise a working volume from around 15 ml.

The receptacle may be a bag for storing biomaterial.

There are significant advantages associated with the present invention.Electrode polarisation between electrodes in direct contact with a testsample is non-linear and depends upon current density. A barrier howeveris more predictable in this regard. In addition, it is beneficial to beable to analyse a test sample whereby contamination is undesirable, andthe ability to analyse the test sample without making direct physicalcontact means that a sample can be analysed without for example removingfrom a receptacle. For example, a test sample such as blood can betested for live cells without transferring to another receptacle oropening the receptacle to allow direct contact.

That is to say, the apparatus may enable a test sample to be analysedwithout direct physical contact with the surface of a measuringelectrode. This is advantageous because contamination of the electrodesand the test sample can be avoided and the shelf life of the measuringelectrodes can be extended.

The measuring arrangement may measure across any suitable distance oftest sample dependent upon the application of the apparatus. For examplethe receptacle for holding the test sample and electrode size may affectthe suitable distance.

The thickness of the receptacle wall is preferably between 0.1 mm and 7mm, preferably between 0.1 mm and 3 mm, preferably between 0.1 mm and 1mm, and even more preferably between 0.3 mm and 1 mm. A typicalthickness of a receptacle such as a flexible polymeric bioreactor issubstantially 0.5 mm.

The receptacle may comprise a span between opposing walls for receipt ofthe test sample, and the thickness of a receptacle wall is between 4%and 0.005% of the span. Thus, the span is significantly greater than thethickness of the receptacle walls. For example, the wall thickness maycomprise 0.5 mm and the span 15 mm, giving a wall thickness of around 3%of the span. In alternative applications the span may be in the order of1 m with a similar wall thickness, giving a wall thickness of around0.005% of the span. As the span increases, it will be appreciated thatinstead of first and second electrodes of each electrode pair beingpositioned externally of opposing walls, the electrodes may bepositioned externally of the same wall. In this case current flowsacross the test medium between the first electrode pair generally in anarc. Voltage is also measured across the test medium between electrodesexternal of the same wall. So for example, in the event of a span of 1m, measurement is not necessarily made across the greatest span.

The receptacle is beneficially non-conductive.

An apparatus according to any preceding claim wherein the apparatuscomprises agitation means for agitating the test sample.

The apparatus preferably further comprises a support arrangement forsupporting the receptacle, where the support arrangement carries thefirst and second electrode pair to define a zone wherein the first andsecond electrode pair contact the receptacle when supported by thesupport arrangement. The first and second electrode pair are preferablyin a fixed location on the support arrangement. The receptacle andsupport arrangement are preferably configured to cooperate such thatthere is direct contact between the electrode pairs and the receptacle.

The support arrangement is preferably configured to receive thereceptacle into the zone. The zone preferably comprises a receivingzone.

The first electrodes may be positioned such that they are substantiallydiametrically opposing each other across the receiving zone, andpreferably wherein the second electrodes are positioned such that theysubstantially oppose each other across the receiving zone.

The support arrangement may cradle the receptacle. Alternatively or inaddition the support arrangement is arranged to be positioned over thetop of the receptacle.

The support arrangement beneficially contains the electrodes of thefirst and second electrode pair.

The support arrangement may comprise multiple zones comprising a supportarrangement array. Thus, multiple receptacles may be received fortesting multiple test samples.

In an embodiment there may further be provided means to agitate thereceptacle. This causes the test sample to be mixed during testing toprevent settling of the test sample and therefore inaccurate measurementdoes not occur. The agitation may be caused by an arrangement whichrocks the sample so as to cause the sample to have a more evenconsistency.

The support arrangement may be arranged to cradle the receptacle. Thisis beneficial in the event that the test sample is supplied in aflexible receptacle. The receptacle may seat onto the supportarrangement. The support arrangement may comprise a platform for receiptof the receptacle. The electrodes are preferably positioned such thatthe receptacle sits onto the electrodes. Therefore, in an operativeposition the receptacle may sit onto the electrodes. The electrodes maybe upwardly facing and preferably outwardly facing.

The support arrangement may comprise a base and sidewalls defining acavity forming the zone for receipt of the receptacle. The electrodes ofeach electrode pair are preferably positioned on the sidewalls havingexposed electrode surfaces in the cavity. This means that a receptaclecontaining the test sample may be located into the cavity and thereceptacle will be in direct contact with the electrodes. The electrodepair are preferably disposed such that current is passed through thecavity between the electrodes, and voltage is measured across thecavity.

In an embodiment of the invention the receptacle may comprise a base andsidewalls defining a cavity for receipt of the test sample, thesidewalls having an inner and an outer surface, and the electrode pairare disposed on the outer surface. The electrode pair are preferablydisposed such that current is passed through the cavity.

In order to optimise the ability to measure the voltage of the testsample through the barrier, it is beneficial to design the electrodepair appropriately. A challenge is to measure an adequate signal withoutrequiring input of too high an excitation voltage. An upper voltagelimit may be in the order of 50V. This can in part be achieved throughproviding a larger contact electrode surface area in contact with thebarrier than is typical for electrodes used for direct contact with atest sample.

That said, the efficacy of the apparatus is determined by any one ormore of barrier thickness, contact electrode surface area andoperational convenience and the shielding of the electrodes fromunwanted electrical fields. Any suitable arrangement of electrodes wouldachieve the advantages set out above.

The contact electrode surface area may be between 1 cm² and 50 cm² whenthe barrier comprises a polymeric bag. However, there is a trade-offbetween the thickness of the barrier and the contact area. For thinbarriers, contact electrode surface may be of the order of squaremillimetres. Thin barriers may be formed using any suitable techniquesuch as, for example, chemical vapour deposition and may be of the orderof microns in thickness.

The first electrode pair each have a barrier contact surface area andthe second electrode pair each have a sensing surface area. The secondelectrode pair may have a sensing surface area less than the barriercontact surface area of the first electrode pair.

The barrier contact surface area of at least one of the first electrodepair and the sensing surface area of at least one of the secondelectrode pair are separated from each other. The barrier contactsurface area of one of the first electrode pair electrodes may bearranged to at least partially surround the sensing surface area of oneof the electrodes of the second electrode pair. It will be appreciatedthat the second of the first electrode pair of electrodes may also bearranged to at least partially surround the sensing surface area of thesecond electrode of the second electrode pair. One or each of the secondelectrode pair may be completely surrounded by the correspondingelectrode of the first electrode pair.

There is a balance to be struck between maximising the voltage signal tobe measured for the input excitation current which is dependent on thespacing between the first electrode pair and also the possibility ofdirect coupling between the first and second electrode pair. As such,with the relative position of the first and second electrodes of thefirst and second electrode pair respectively, current driven through thefirst electrode pair adds to the voltage drop across the secondelectrode pair which improves measurability. That is to say, therelative positions of the first and second electrodes in the first andsecond electrode pair can be optimised to maximise the sensed voltagefor a given excitation current.

It will be appreciated that as presented herein any of the preferred oroptional features for positioning of the electrode pair may also beapplicable to the second electrode pair.

One or more shielding arrangements are preferably provided for shieldingeach of the respective second electrodes from charge resulting from theapplication of the excitation current by the first electrode pair. Thisprevents stray current contaminating the signal determined by themeasuring arrangement. The second electrodes preferably have a sensingsurface area and a non-sensing surface area, and the or each shieldingarrangement may be positioned around the non-sensing surface area. Thesensing area can be described as area of electrodes that is uncovered,and preferably contacts the receptacle wall in an operableconfiguration. The or each shielding arrangement is preferablypositioned at least partially in the support arrangement to provide abarrier between the first electrodes and second electrodes.

In an embodiment of the invention, the first and the second electrodepairs are arranged to adhere to the receptacle. Accordingly, a user mayposition the electrodes as required onto a receptacle in desiredlocation. The electrodes may comprise an adhesive material. Theelectrodes may be carried by a support that may carry one of theelectrodes of each pair, and may comprise a second support for carryingthe other of the first and second electrode.

The first and second electrode pairs may mountable and demountable tothe receptacle.

Also according to the present invention there is an apparatus foranalysis of a dielectric test sample, the apparatus comprising:

-   -   a first electrode pair for application of an excitation current        to a test sample;    -   a measuring arrangement for measuring voltage across a test        sample comprising a second electrode pair; and    -   a support arrangement for carrying the first and second        electrode pair, the support arrangement configured to define a        zone to support a receptacle for carrying the test sample such        that the receptacle is in communication with the first and        second electrode pair when in the zone.

The support arrangement is preferably configured to receive thereceptacle into the zone.

The first electrodes are preferably positioned such that they aresubstantially diametrically opposing each other across the zone, andpreferably wherein the second electrodes are positioned such that theysubstantially oppose each other across the zone.

The support arrangement may be arranged to cradle the receptacle.

The support arrangement may be arranged to be positioned over the top ofthe receptacle.

The support arrangement may contain the electrodes of the first andsecond electrode pair.

The support arrangement may comprise multiple zones comprising a supportarrangement array.

The apparatus may comprise one or more shielding arrangements forshielding each of the respective second electrodes from charge resultingfrom the application of the excitation current by the first electrodepair.

The second electrodes may have a sensing surface area and a non-sensingsurface area, and the or each shielding arrangement is positioned aroundthe non-sensing surface area.

The or each shielding arrangement may be positioned at least partiallyin the support arrangement to provide a barrier between the firstelectrodes and second electrodes.

The test sample may be dielectric.

The first and second electrodes may be stuck onto the receptacle usingan adhesive layer.

The support arrangement is beneficially arranged to receive a testsample carrying receptacle. The support arrangement may cradle a testsample carrying receptacle.

According to a further aspect of the invention there is a method ofanalysing a test sample, the method comprising:

-   -   applying an excitation current to the test sample provided in a        receptacle using a first electrode pair and measuring voltage        across the test medium using a second electrode pair, wherein        the receptacle comprises a receptacle wall that forms a barrier        between the first and the second electrode pair and the test        sample; and    -   determining one or more properties of the test sample derived        from the measured voltage.

It will be appreciated that the current flow between the first electrodepair is also beneficially measured and used in determination of theproperties of the test sample.

A support arrangement is also preferably provided for supporting thereceptacle, where the support arrangement carries the first and secondelectrode pair to define a zone wherein the first and second electrodepair contact the receptacle when supported by the support arrangement,and the method preferably comprises positioning the receptacle in thezone.

Apparatus and methods are preferably apparatus and methods formeasurement of biomass.

BRIEF DESCRIPTION OF THE DRAWINGS

Aspects of the present invention will now be described by way of exampleonly with reference to the accompanying Figures where:

FIG. 1 is a schematic representation of a side view of an illustrativeembodiment of the present invention.

FIG. 2 is a schematic representation of a side view of an illustrativefurther embodiment of the present invention.

FIG. 3 is a schematic representation of a side view of an illustrativefurther embodiment of the present invention.

FIG. 4 is a schematic representation of a side view of an illustrativefurther embodiment of the present invention.

FIG. 5 is a schematic circuit diagram representing the provision of abarrier between the single electrode pair and the test sample, where thevoltage is measured across the electrode pair.

FIG. 6 is a schematic circuit representation of the provision of abarrier between a first electrode pair for supplying current to the testsample and a second electrode pair for measuring voltage across the testsample.

FIG. 7 is a schematic illustrative representation of an electrodeconfiguration for application with any of the embodiments presented.

FIG. 8 is a schematic illustration of an electrode configuration wherebythe measuring electrodes are shielded by metal enclosures to preventcontamination from the electrode pair in accordance with any embodiment.

FIG. 9 is a schematic illustration of the capacitance values that arerealised for different test samples using an illustrative embodiment ofthe present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIG. 1 there is a schematic representation of anillustrative embodiment of the present invention. A receptacle 2 isprovided which is illustrated as a flexible bag but may take a solidform which in turn is received into a support arrangement 4 defining azone in the form of a cavity 6. The receptacle wall forms the barrierbetween the test sample within the receptacle 2 and the electrodes. Afirst electrode pair 8 a,8 b are presented in addition to a measuringarrangement utilising a second electrode pair 10 a,10 b. The firstelectrode pair 8 a, 8 b are arranged to drive current through the testsample 12 provided within the receptacle 2. The current pathway istherefore from electrode 8 a, through the receptacle wall, through thetest sample, through the receptacle wall on the opposite side of thereceptacle and to the opposing electrode 8 b. That is to say, no directphysical contact between the electrodes and the test sample takes place.

It will be appreciated that multiple support arrangements 4 may beprovided in communication to form an array for testing of multiplesamples concurrently.

This is also presented schematically in FIGS. 5 and 6. A schematicrepresentation of the electrodes 8 and 10 are presented in FIG. 7.

In the embodiment presented the support arrangement 4 is an insulatingmaterial which is a rigid material such as a polymer. The respectiveelectrodes are positioned on the inner surface of the supportarrangement walls 14, and preferably oppose one another in order thatthe test sample is analysed effectively. A means to agitate the testsample such as a rocking device (not shown) for rocking the supportarrangement 4 may be provided.

In the embodiment presented separate measuring electrodes 10 a,10 b areprovided to the excitation electrodes 8 a, 8 b. The measuringarrangement 16 further comprises apparatus to measure the currentthrough the circuit 18 passing through the test sample via the firstelectrode pair and also the voltage across the second electrode pair 10a, 10 b via circuit 20. The voltage drop can be measured from which thespecific capacitance determined thereby providing an indication of theamount of live cells within the test sample.

A similar embodiment is presented in FIG. 2, whereby a flexiblereceptacle 2 is provided and is seated onto a support arrangement 4having exposed first and second electrode pairs 8, 10. The supportarrangement 4 is shown curved to cradle a flexible receptacle 2 in theillustrative embodiment. In this embodiment the electrodes are outwardlyfacing and communicate with the receptacle 2 in operation and thecurrent flowpath is not across the receptacle 2 but is instead throughan arc in the test sample 12. Again, there is no direct contact betweenthe test sample and the electrodes.

Referring to FIG. 3, the barrier in this embodiment is provided by thewall of the receptacle and the test sample 12 is provided in directcommunication with the internal wall of the non-conductive receptacle.The first and, if present, second electrode pair are provided incommunication with the opposing side of the receptacle wall. Thus,measurement of the voltage is made through the receptacle wall. Theelectrodes 8,10 may be carried by a support arrangement to be in contactwith the receptacle wall or may be adhered to the receptacle wall. Thus,the method of testing the sample may comprise either positioning areceptacle containing a test sample into communication with the zone ofthe receptacle in contact with the electrodes 8,10, or alternativelypositioning the electrodes onto the receptacle.

Referring to the embodiment of FIG. 4, a probe 30 is provided for use inthe measurement of the concentration of live biomass. In this embodimentthe probe 30 is inserted into a test sample which may be carried in, forexample, a conduit 32 or a tank or a vessel through which test samplemay flow. The probe 30 has an elongate insulating body portion 34arranged to carry the first 8 a,8 b and second 10 a,10 b electrodepairs. As shown in the illustrative embodiment again first and secondelectrode pairs are represented, although voltage can also be measuredacross the first electrode pair 8 a,8 b only. The second electrode 8 bof the first electrode pair (and second electrode of the secondelectrode pair 10 b) is shown in dashed lines as is provided on theopposing side of the body portion 34. The elongate body portion 34 has alongitudinal length extending to a tip in a longitudinal axis whereinthe first and second electrode pairs extend lengthwise towards the tip36 in the longitudinal axis. An insulating coating or cover 38 acts as abarrier between the body portion 34, and in particular the electrodes,and the test sample meaning that the probe body is not in direct contactwith the test sample. The electrodes may also be positioned along thelength of the elongate body portion 34 to form what would resemble ringsaround the elongate body portion 34.

Referring to FIG. 5 there is a schematic representation of utilising asingle electrode pair 8 a,8 b for input of an excitation current into atest sample and also using the same electrodes 8 a,8 b for measurementof voltage (in order that voltage drop can be determined) across thetest sample. The schematic diagram shows the test sample 12 and barrierwhich may be in the form of a wall of a receptacle 2 or a coating 38 ona probe. Electrode pair 8 a,8 b are utilised to input excitation currentfrom source 40. Voltage is measured across the electrodes 8 a,8 b atreference numeral 42 and current is amplified and measured at numeral44. In such an embodiment it can be difficult to achieve accuratemeasurement of current and voltage if there is any change associatedwith the receptacle/barrier 2 such as movement relative to theelectrodes 8 a,8 b.

Referring to FIG. 6, a schematic representation is made of the circuitfrom the perspective of current input and voltage measured. In thisalternative embodiment, a first electrode pair is utilised for inputcurrent to the test sample, and a second electrode pair is utilised formeasurement. The AC power source 40 supplies current through the barrierrepresented by capacitors 46 and through the test sample 12. The testsample 12 can be represented as resistor-capacitor network 50. The smallcapacitors are indicative of live cells due to the live cells notbecoming polarised under the applied current. Measurement of current ismade using the left side of the circuit via the test sample 48 and theright side of the circuit representative of the voltage measurementside, where the voltage is measured through the barrier 46 asschematically represented as large capacitors 52 compared to those ofthe cells as represented by capacitors 50. The voltage is measuredthrough a differential amplifier 54 with a high input impedance. This isnecessary to enable measure of what is effectively an extremely smallcapacitance of the cells. Measurement is being made of the voltagethrough the receptacle meaning an extremely small phase shift ismeasured. If measured without utilising such a differential amplifierwith high input impedance then the input current to the measuring devicewould cause a phase shift thereby significantly affecting measurementability. The provision of an ‘infinite’ impedance differential amplifieris therefore used for measurement. The circuit will also need to haveappropriate compensation for the common mode rejection of the amplifier.The common mode rejection can be achieved using any known means.

Referring now to FIG. 7, there is a schematic representation in planview of a first 8 a,8 b and second 10 a,10 b electrode pair. The firstelectrode pair 8 a,8 b each have a barrier contact surface area 8 c, 8 dwhich in an operable configuration communicate with the receptacle, andthe second electrode pair 10 a, 10 b each have a sensing surface area 10c,10 d also for communicating with the receptacle, where the contactsurfaces are presented in FIG. 8. The second electrode pair 10 a,10 bmay comprise a sensing surface area less than the barrier contactsurface area of the first electrode pair. The barrier contact surfacearea of one of the first electrode pair electrodes is shown arranged tosurround the sensing surface area of one of the electrodes of the secondelectrode pair. The second of the first electrode pair of electrodes isalso arranged to surround the sensing surface area of the secondelectrode of the second electrode pair. As an illustrative embodimentonly, the electrode dimensions 8 a and 8 b is 50 mm×100 mm with a widthof 10 mm. The electrode dimensions of 10 a and 10 b are 10 mm×50 mm. Thespan between the electrodes is 12 mm.

FIG. 8 illustrates an embodiment where metal shield members 102 and 104are used to prevent contamination of stray electrical charge fromelectrodes 8 a and 8 b into the electrodes 10 a and 10 b before thedetermination of the voltage V in the differential amplifier 106. Theelectrodes 8 a, 8 b, 10 a and 10 b are carried by a support arrangement4 such that sensing surface areas 10 c and 10 d of respective electrodes10 a and 10 b and the barrier contact areas 8 c and 8 d of theelectrodes 8 a and 8 b communicate with the receptacle 2 in operation.The shield members 102 and 104 enclose the electrodes 10 a and 10 b sothat as current flows between electrodes 8 a and 8 b stray currentcontaminating the signal measured at the differential amplifier 106 isprevented. The shield members 102 and 104 are grounded so that they donot transfer interfering voltage to electrodes 10 a and 10 b.

FIG. 9 illustrates the capacitance values that are obtained for firstand second test samples in accordance with an illustrative embodiment ofthe invention comprising respectively water mixed with salt and yeast(dashed lines) and water mixed with just salt (solid lines). It will beevident that different capacitance values are realised at differentfrequencies for each respective test sample. Measurements for plottingof the lines in FIG. 9 were made using the electrode configuration aspresented in FIG. 7, with a span between electrodes of 12 mm and areceptacle with wall thickness of 0.5 mm.

That is to say, the measuring apparatus 16 receives the voltagemeasurements from the measuring electrodes 10 a and 10 b and uses themto determine the capacitance of the test sample. The capacitance isindicative of the contents of the test sample and in FIG. 9, thedifference between water mixed with salt and water mixed with salt andyeast is illustrative of the effect that the presence of yeast over alarger range of frequencies.

Aspects of the present invention have been described by way of exampleonly and it will be appreciated to the skilled addressee thatmodifications and variations may be made without departing from thescope of protection afforded by the appended claims.

1. An apparatus for analysis of a test sample comprising: a firstelectrode pair for application of an excitation current to a testsample; a measuring arrangement for measuring voltage through the testsample comprising a second electrode pair; and a receptacle for receiptof the test sample, where the receptacle comprises a receptacle wallthat forms a barrier between the first and second electrode pair and thetest sample such that the receptacle wall contacts both the first andsecond electrode pairs and the test sample when the apparatus is in anoperable state. 2-31. (canceled)